PDE 5 inhibitors are broken down primarily by enzyme, cytochrome P450enzyme CYP3A4. Medications that decrease or increase the activity of CYP3A4 may affect levels and effectiveness of PDE 5 inhibitors. Such drugs include medications for the treatment of HIV (protease inhibitors) and the antifungal medications ketoconazole and itraconazole. Thus caution is recommended.


If on one hand, depression and anxiety can lead to ED, drugs commonly used for their treatment can cause ED, as well. Sexual dysfunctions are common side effects of several psychotropic drugs that can disrupt sexual health by several different mechanisms (83). In particular, ED has been reported in subjects using serotonin selective re-uptake inhibitors (SSRI), lithium and benzodiazepines (83). SSRI are associated with a broad spectrum of sexual dysfunctions, but the most commonly reported complaints are delayed ejaculation or anorgasmia and reduced sexual desire (84). Several mechanisms could be advocated including the agonist effect on serotonin receptors type 2 and the increase in PRL levels. ED is a frequent complaint as well (84,85). The relationship between the use of SSRI and ED can be secondary to loss of sexual desire but SSRI, in particular paroxetine, are also able to inhibit cholinergic receptors and nitric oxide synthase (86). In addition, it has been observed that SSRIs might down-regulate hypothalamic-pituitary-testis axis in depressed men (87).
Other medical therapies under evaluation include ROCK inhibitors and soluble guanyl cyclase activators. Melanocortin receptor agonists are a new set of medications being developed in the field of erectile dysfunction. Their action is on the nervous system rather than the vascular system. PT-141 is a nasal preparation that appears to be effective alone or in combination with PDE5 inhibitors. The main side effects include flushing and nausea. These drugs are currently not approved for commercial use.
Nerve or spinal cord damage: Damage to the spinal cord and nerves in the pelvis can cause erectile dysfunction. Nerve damage can be due to disease, trauma, or surgical procedures. Examples include injury to the spinal cord from automobile accidents, injury to the pelvic nerves from prostate surgery for cancer (prostatectomy), and some surgeries for colorectal cancer, radiation to the prostate, surgery for benign prostatic enlargement, multiple sclerosis (a neurological disease with the potential to cause widespread damage to nerves), and long-term diabetes mellitus.
A full battery of labs was ordered and returned normal. A PCDU was ordered which revealed normal arterial inflow with velocities greater than >40 cm/sec with increased end diastolic velocities suggestive of venous leak. After pharmacologic erection, he developed a partial erection that resolved within 1 minute. This was consistent with a diagnosis of venous leak impotence. Pharmacologic cavernosography was performed and revealed bilateral crural leakage. He underwent infrapubic bilateral crural ligation of the penis, which cured his ED. The patient returned to clinic 6 months later with recurrent impotence. A pharmacologic cavernosography revealed recurrent venous leak. Additional crural ligation via a perineal approach was performed. Two months later he reported normal penile erections, and the result has lasted for more than 5 years. He continues to follow up annually in clinic.
It's also important to remember that your mental health plays as much a part of your sexual ability as your physical health. Stress and other mental health concerns can cause or make erectile dysfunction worse. Minor health problems may slow your sexual response, but the accompanying anxiety that comes with the slow sexual response can shut things down entirely.
Monitoring erections that occur during sleep (nocturnal penile tumescence) can help you and your doctor to understand if the erectile dysfunction is due to psychological or physical causes. The nocturnal penile tumescence test is a study to evaluate erections at night. Normally men have three to five erections per eight hours of sleep. The test can be performed at home or in a sleep lab. The most accurate way to perform the test involves a special device that is connected to two rings. The rings are placed around the penis, one at the tip of the penis and the other at the bottom (base) of the penis. The device records how many erections occur, how long they last, and how rigid they are. The test is limited in that it does not assess the ability to penetrate.
Andrew McCullough, MD, associate professor of clinical urology and director, male sexual health program, New York University Langone Medical Center. Lecturer: Auxillium. Research grant: Pfizer. Data safety monitoring board: Pfizer. Consultant: Slate Pharmaceuticals. Clinical trials: Warner Chilcott, Vivus, Lilly, Bayer-GSK, ICOS, Timm, Schering Plough, Aeterna.
Capogrosso, P., Colicchia, M., Ventimiglia, E., Castagna, G., Clementi, M. C., Suardi, N., … Salonia, A. (2013, May 7). One patient out four with newly diagnosed erectile dysfunction is a young man - worrisome picture from the everyday clinical practice [Abstract]. Journal of Sexual Medicine, 10(7),1833-41. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23651423
The penis contains three cylinders, the two corpora cavernosa, which are on the top of the penis (see figure 1 below). These two cylinders are involved in erections. The third cylinder contains the urethra, the tube that the urine and ejaculate passes through, runs along the underside of the penis. The corpus spongiosum surrounds the urethra. Spongy tissue that has muscles, fibrous tissues, veins, and arteries within it makes up the corpora cavernosa. The inside of the corpora cavernosa is like a sponge, with potential spaces that can fill with blood and distend (known as sinusoids). A layer of tissue that is like Saran Wrap, called the tunica albuginea, surrounds the corpora. Veins located just under the tunica albuginea drain blood out of the penis.

Patients should continue testosterone therapy only if there is improvement in the symptoms of hypogonadism and should be monitored regularly. You will need periodic blood tests for testosterone levels and blood tests to monitor your blood count and PSA. Testosterone therapy has health risks, and thus doctors should closely monitor its use. Testosterone therapy can worsen sleep apnea and congestive heart failure.
Is your erectile dysfunction due to psychological (stress, relationship problems, etc.) or physical factors? Your doctor may ask if you note erections at night or in the early morning. Men have involuntary erections in the early morning and during REM sleep (a stage in the sleep cycle with rapid eye movements). Men with psychogenic erectile dysfunction (erectile dysfunction due to psychological factors such as stress and anxiety rather than physical factors) usually maintain these involuntary erections. Men with physical causes of erectile dysfunction (for example, atherosclerosis, smoking, and diabetes) usually do not have these involuntary erections. Men with psychogenic erectile dysfunction may relate the onset of problems to a "stressor," such as failed relationship. Your doctor may suggest a test to determine if you have erections during sleep, which may suggest that there may be a psychological cause of the erectile dysfunction.
Cigarette smoking is a risk factor for ED, according to the 2014 Report of the U.S. Surgeon General. Excess weight can also contribute to erectile dysfunction. A 2004 Italian study found that one-third of their 110 obese study subjects were able to eliminate their erectile dysfunction problems by losing fifteen percent of their weight through diet and exercise.
To understand what happens in ED, it's helpful to know some anatomical basics. When aroused by either sensory or mental stimuli, the brain sends a signal through the nerves to the penis, causing the muscles there to relax. This opens up space for blood to flow in and engorge the penis. A membrane within the penis traps blood inside to help maintain the erection, which subsides when the penile muscles contract, forcing blood back into the rest of the body. Any number of things can go wrong in this process, leading to erectile dysfunction.

In the short term, alcohol relaxes muscles in the penis, letting blood to flow in (which is a good thing). However, alcohol also prevents other blood vessels from closing and trapping all the extra blood. Erections depend on trapping increased blood flow in the erectile tissue of the penis. If you don’t trap that extra blood, you don’t get an erection. In the long run, excessive alcohol consumption can cause liver scarring, high blood pressure, and can damage your blood vessels resulting in erectile dysfunction.

In many of these cases, a discussion between the physician, the man with erectile dysfunction, and possibly his partner can help to resolve the issues leading to treatment failure. For men who experience severe side effects, can’t take the drugs for other reasons (such as taking medicines such as nitroglycerin), or don’t respond in spite of further education on the correct use of the drugs, there are other treatment options that can help most men remain sexually active.
Drinking in moderation can be beneficial to your heart health, and therefore your sex life. A 2004 study published in the journal Seminars in Vascular Medicine found moderate alcohol consumption was associated with decreased cardiovascular mortality due to the antioxidant capacities of alcoholic beverages. The polyphenolic compounds — a group of compounds that include tannins and anthocyanins — were shown to change the lipid profiles, decrease coagulation, increase fibrinolysis, inhibition of platelets, and increase nitric oxide. This is vital since vascular diseases (those that affect the blood vessels) commonly cause erectile dysfunction.
When we say it’s a barometer of men’s health, it’s a signal. It’s an indicator that things may be right or not. And so when a man develops an erectile problem– and we’re talking about something that is occurring over time. It’s not something that just occurred overnight. When it occurs overnight, it’s more often than not a psychogenic, an anxiety reaction.
As you can imagine, these symptoms can make it difficult to take pleasure in much of anything, let alone sex. A study published in a 1998 edition of Psychosomatic Medicine shows a clear link between depression and erectile dysfunction in men. Using data obtained from the Massachusetts Male Aging Study, researchers were able to conclude that a relationship between depressive symptoms and erectile dysfunction existed and was independent of aging and demographics.
Researchers have found that one particular simple sugar, present in increased levels in diabetics, interferes with the chain of events needed to achieve and maintain erection and can lead to permanent penile impairment over time.  The results, which have implications for new types of erectile dysfunction treatments targeting this mechanism of erection, are described in the August 16 issue of the Proceedings of the National Academy of Sciences.
Combination therapy has proven effective for some men who don’t respond adequately to oral medicines. The idea is to use two drugs with different mechanisms of action for better results. Commonly, sildenafil is used in combination with pellets of alprostadil (synthetic prostaglandin E1) that are inserted into the urethra (the tube in the penis that carries urine from the bladder to the outside of the body). Alprostadil also increases the blood supply to the penis, but by different means.
Luckily, awareness of ED as a significant and common complication of diabetes has increased in recent years, mainly because of increasing knowledge of male sexual function and the rapidly expanding armamentarium of novel treatments being developed for impotence. Studies of ED suggest that its prevalence in men with diabetes ranges from 35–75% versus 26% in general population. The onset of ED also occurs 10–15 years earlier in men with diabetes than it does in sex-matched counterparts without diabetes.
L-arginine is an amino acid that occurs naturally in the human body and helps make that magic nitric oxide so important for supporting an erection. A 1999 study observed the effects of six weeks of L-arginine administered daily among men with ED. One third of those who took five grams per day of L-arginine experienced significant improvements in sexual function.
Diabetes, high blood pressure (hypertension), elevations in blood lipids or cholesterol are considered blood vessel problems and have all been associated with Erectile Dysfunction. The blood vessel abnormalities caused by these diseases affect vessels throughout the body and often produce other symptoms of vascular diseases. Diabetics and patients with hypertension frequently have heart disease. These conditions typically interfere with the ability of the penile vessels to work properly and ultimately cause ED.
• Blood Vessels: Diabetes damages blood vessels, especially the smallest blood vessels such as those in the penis. Diabetes can also cause heart disease and other circulatory problems. Proper blood flow is absolutely crucial to achieving erection. “Erection is a hydraulic phenomenon that occurs involuntarily,” says Arturo Rolla, MD, of Harvard University School of Medicine. “Nobody can will an erection!” Anything that limits or impairs blood flow can interfere with the ability to achieve an erection, no matter how strong one’s sexual desire.
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